Human intestine grown in mice could optimize your gut

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The smooth operation of a healthy bowel is something most of us take for granted, but for the many who are born with an abnormally short intestine, those who have had significant portions of it removed, or have Crohn’s disease or ulcerative colitis, life is no picnic. Researchers from the Children’s Hospital of Los Angeles have developed a way to regenerate a new gut, or at least parts of it, from existing cells. The trick is to gently harvest healthy cells from the patient, seed them on to a special polymer matrix, and then temporarily implant them inside the abdominal cavity of a mouse where they can mature.

After four weeks of mouse living, the transplanted cells develop into a spherical sector of intestine which the researchers called an organoid. This tissue-engineered small intestine can then potentially be transplanted back into the patient to cure their ills. The advantage here over using gut material donated from someone else is that the patient conveniently side-steps a life-long sentence of drug induced immunosuppression — a necessary precaution to avoid rejection that leaves them susceptible to all kinds of opportunistic infections.

In order to be a true gut, the researchers had to demonstrate that the new tissue not only looks like gut, but also acts like gut. The organoids were found to contain all the essentials a true intestinal wall needs — digestive enzymes, microvilli (little feet that greatly increase the surface area of nutrient absorption), muscle cells, and stem cells to replenish the ranks. The transplants also were found to contain the signature mucus-secreting “goblet cells,” and were even able to break down complex sugars into simple glucose.

The concept of using other animals as temporary bastions in which to grow tissue for humans is not new. Astrocytes from the human brain have previously been shown to proliferate when transplanted into the smooth cortex of the mouse. Other researchers have even genetically transformed the surface of the mouse brain to look more like the deeply fissured cortex of humans. But we are not necessarily barbarians here. The idea, at least hopefully, is not to use animals as long-term surrogates and bioreactors to grow new organs, but rather just as temporary incubators where researchers can better figure out what is going on with cells without having to subject humans to the full ordeal.

This may be a good place to mention an intriguing new discovery revealing a deep connection between the brain and gut. One kind of gut cell that the researchers probably didn’t find in their organoids is the enteroendocrine cell. That’s because it was only discovered a few weeks ago. None-the-less these cells are now known to play a critical role in relaying information from the gut to the brain. They are actually very similar in character to neurons and have a unique giant appendage known as a neuropod. Using their neuropod as a direct portal to the nervous system, these cells can transmit various viruses up to brain for better or for worse.

While many of us have a healthy gut, it is not necessarily always the optimal gut. Evolution has repeatedly demonstrated its ability to transform a short carnivorous gut into a long and winding composter for a vegetable diet in relatively short periods of time. Similarly, as the more enlightened vegetarians among us try to adapt to a less energy-rich diet, a few extra intestinal modules could come in handy.

As the rest of us continue to feast on smoked and processed meats, and accrue the inevitable clockwork mutations that lower us down towards the inescapable abyss of colonic malady and cancer, it is comforting to known that help in the form of new organoids may be on its way.

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